We have previously shown that bleomycin induced pulmonary fibrosis in the rat is useful model of chronic lung inflammation associated with development of fibrosis. In view of strong evidence suggesting genetic restriction in the development of pulmonary fibrosis, in humans as well as in mice, we propose to adapt and evaluate the bleomycin model in mice. Following evaluation of the basic biochemical, immunologic and inflammatory parameters of the model in mice, we will exploit the ready availability of large numbers of genetically well-defined inbred, cogenic resistant and recombinant-inbred mouse strains, to help identify and define the genetic marker(s) associated with the development of bleomycin-induced pulmonary fibrosis. Preliminary evidence suggests the existence of such markers. By correlating the intensity of the fibrotic response with the extent of change in the biochemical, immunologic and inflammatory parameters as a result of genotype (and bleomycin treatment), we hope to provide more unambiguous insights into the mechanism by which bleomycin causes pulmonary fibrosis. Furthermore, the results of this study should help explain the pathogenesis of other forms of pulmonary fibrosis, since fibrosis is a stereotyped response independent of initial cause.